a study of ol-101 injection in patients with relapsed or refractory multiple myeloma (rrmm)

Conditions: Multiple Myeloma

Summary: this clinical trial aims to characterize the safety of ol-101 and establish the recommended dose for future research and to evaluate the efficacy of ol-101 (dose expansion).

this study will evaluate the safety and efficacy of ol-101, a chimeric antigen receptor t cell (car-t) therapy directed against b-cell maturation antigen (bcma) and g protein-coupled receptor class c group 5 member d (gprc5d). this study is a single-arm, open-label, early exploratory clinical trial, conducted in two phases: dose escalation and dose expansion in adults with multiple myeloma. the trial begins with the dose-escalation phase that focus on safety and tolerability, with interval assessments for potential dose escalation or de-escalation. recommended dose will be selected at the completion of the dose escalation stage in the dose expansion stage. the study aims to assess safety, pharmacokinetic/pharmacodynamic profiles, and efficacy.

Eligibility criteria:
inclusion criteria: * documented diagnosis of multiple myeloma according to the 2014 imwg diagnostic criteria * relapsed/refractory multiple myeloma as defined by: 1) received at least 3 prior lines of mm treatment (must include a pi, an imid, and an anti-cd38 antibody). 2）disease progression within 12 months of the most recent anti-mm therapy; or disease progression within the past 6 months and subsequently lack response to the most recent line of therapy. * measurable disease at screening as defined by any of the following: 1. serum monoclonal paraprotein (m-protein) level ≥1.0 g/dl or urine m-protein level ≥200 mg/24 hours; or 2. light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain ≥10 mg/dl and abnormal serum immunoglobulin kappa lambda free light chain ratio. * positive expression of either bcma or gprc5d on bone marrow plasma cells; must be gprc5d expression positive if previously received bcma targeted therapy * ecog 0-1 * expected life expectancy exceeds 12 weeks * adequate bone marrow reserve or organ function meeting the following criteria: 1. hemoglobin ≥ 70 g/l 2. platelet count ≥ 50 × 10\^9/l 3. absolute lymphocyte count ≥ 0.3×10\^9/l 4. absolute neutrophil count ≥ 1.0 × 10\^9/l 5. alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 2.5 times the upper limit of normal (uln) 6. total bilirubin ≤ 2 times uln; except in subjects with congenital bilirubinemia (such as gilbert syndrome, in which case the direct bilirubin ≤1.5 × uln is required) 7. creatinine clearance ≥ 60 ml/min (calculated by cockcroft-gault equation). 8. corrected serum calcium ≤12.5 mg/dl (≤3.1 mmol/l) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/l) 9. spo2\>92% on room air 10. left ventricular ejection fraction (lvef) ≥ 50% as assessed by echocardiogram; no clinically meaningful pericardial effusion by ultrasound exclusion criteria: * solitary plasmacytoma * known active central nervous system (cns) involvement or exhibits clinical signs of cns involvement of multiple myeloma. * received allogeneic stem cell transplant; received autologous stem cell transplant within 12 weeks before screening * active second primary malignant tumor, exclude the following: cured non- melanoma skin cancer, non-metastatic prostate cancer, cervical carcinoma in situ, ductal or lobular carcinoma in situ of the breast * any other significant medical disease, abnormality, or condition that, in the investigator judgment, may make the patient unsuitable for participation in the study or put the patient at risk. * plasma cell leukemia, waldenström's macroglobulinemia, poems syndrome, or primary al amyloidosis.

Keywords: ol-101 multiple myeloma phase 1 single arm